Short Chain Fructo Oligosaccharides

Endpoint summary

Description of key information

Oral route:

A study performed according to a method similar to OECD 420 guideline was carried out with ScFOS (Manish et al 2018). In this study, the test item was administered as a single oral dose at the dose levels of 2000, 5000, and 9000 mg/kg to rat male /and female (n= 5 rats/sex/group). As a results, no clinical signs, no mortality, no gross pathological abnormalities, no effects on body weight and feed consumption at any dose level were observed. The LD50 was > 9000 mg/kg bw (Highest dose tested).

 

Two others studies were performed by oral route on rat and mice (Takeda et al 1982).

• On rat Sprague-Dawley rats male and female (n = 6 rats/group),  LD50 for oral administration of ScFOS in this study was > 9000 mg/kg bw.


• On JcL-IcR mice (n = 6 mice/group), LD50 for oral administration of ScFOS in this study was > 9000 mg/kg bw.

Dermal route:

A study performed according to a method similar to OECD 402 guideline was carried out with ScFOs (CRL 2021). In this study, ScFOs was administered to a single female Wistar Han rat by a single dermal application at 2000 mg/kg body weight for 24 hours in a range finder study.Based on the results, the main study was performed by dosing two additional females at 2000 mg/kg. As a results, no mortality, no signs of systemic toxicity, no abnormalities at macroscopic postmortem, were observed at any dose level. The body weight gain shown by the animals during the observation period was within the range expected for rats used in this type of study. The LD₅₀ determined in the GLP guideline dermal  toxicity study performed on female rats was greater than 2000 mg/kg bw.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

not specified

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

FOS (FOSSENCE TM) used for the experiments was provided by Tata Chemicals Limited (Tamilnadu, India) and stored at ambient conditions (>15°C to <25°C).

- CAS no. 308066-66-2
- Composition (on dry basis)
- FOS: 95.46%
a) 1-Kestose (GF2): 40.23%
b) Nystose (GF3):47.15%
c) 1F-Fructofuranosylnystose (GF4): 8.08%
- Other sugars 4.50%
a) Glycerol: 1.40%
b) Fructose: 0.36%
c) Arabitol: 0.36%
d) Glucose: 0.63%
e) Sucrose: 1.75%
- Physical appearance Fine white powder
- Moisture content (as per CoA): 2.26%

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The test item was mixed in Milli-Q water and administered as a single oral dose at the dose levels of 2000, 5000, and 9000 mg/kg
5 Wistar rats of each sex were randomly assigned to 4 groups (control, 2000, 5000, and 9000 mg/kg).

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Milli-Q water.

Details on oral exposure:

The highest dose of 9000 mg/kg was considered as maximum feasible dose from oral administration perspective considering high viscosity factor and dose volume.
The dose volume employed was 15 mL/kg body weight.

Doses:

2000, 5000, and 9000 mg/kg

No. of animals per sex per dose:

n= 5 rats/sex/group

Control animals:

yes

Remarks:

Milli-Q water was administered to control group rats.

Details on study design:

The rats were observed for clinical signs or mortality, and body weights and feed consumption were measured. All the rats were euthanized under isoflurane anesthesia on day 15, and gross pathological examinations were performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 9 000 mg/kg bw

Based on:

test mat.

Mortality:

Oral gavage administration of test item i did not reveal any mortality at 2000, 5000, and 9000 mg/kg body weight.

Clinical signs:

other: other: other: Oral gavage administration of test item i did not reveal any clinical signs at 2000, 5000, and 9000 mg/kg body weight.

Gross pathology:

Necropsy at the end of study (day 15 post-dose) did not reveal any gross pathological abnormalities.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, Wistar rats did not reveal any clinical signs, mortality, on body weight, and feed consumption at any dose level. No gross pathological abnormalities were also observed after necropsy. The MTD and the LD50 were > 9000 mg/kg bw (Highest dose tested).

Executive summary:

The objective of this study was to evaluate the toxicity of FOS product FOSSENCE^TM following a single oral administration in rats according to methods similar to OECD 420 guidelines. The study was GLP compliant.

The FOSSENCE^TM was mixed in Milli-Q water and administered as a single oral dose at the dose levels of 2000, 5000, and 9000 mg/kg (n=5 rats/sex/group). The highest dose of 9000 mg/kg was considered as maximum feasible dose from oral administration perspective considering high viscosity factor and dose volume.

 

Under the test conditions, Wistar rats did not reveal any clinical signs, mortality, on body weight, and feed consumption at any dose level. No gross pathological abnormalities were also observed after necropsy. The MTD (Maximum Tolerable Dose) and the LD50 were > 9000 mg/kg bw (Highest dose tested).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

9 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 July 2021 - 04 Augustus 2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

2017

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

Identification: Actilight 950P Premium "Fructo-Oligosaccharides"
Substance: Short-chain fructo-oligosaccharides
EC No.: 908-300-1
Appearance: White powder
Purity: 95.4%

COMPOSITION:
scFOS is short chains of fructose molecules linked to a molecule of sucrose (glucose-fructose disaccharide). Thus, scFOS is a multiconstituent substance composed of three oligosaccharides: 1-kestose (GF2), nystose (GF3) and fructosyl-nystose (GF4).
With:
- TOTAL FOS: 95.4 expressed as dry matter
- Kestose (GF2): 39.2% FOS
- Nystose (GF3): 47.6% FOS
- 1F-Fructofuranosylnystose (GF4:) 13.6% FOS
- Glucose +Fructose + Saccharose : 4.6% expressed as dry matter

Species:

rat

Strain:

Wistar

Remarks:

(HAN)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS:

- 3 females (nulliparous and non-pregnant)
- Age at dosing initiation: Young adult animals (approximately 11-12 weeks old)
- Weight at dosing initiation: 168 - 178 g
- Housing: On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.). During the study animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized wooden fibers as bedding material equipped with water bottles. For psychological/environmental enrichment, animals were provided with paper.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), ad libitum.
- Water: municipal tap water, ad libitum.
- Acclimation period: at least 5 days

CONTAMINANT ANALYSIS
Periodic analysis of the water was performed and feed was analyzed by the supplier for nutritional components and environmental contaminants. It is considered that there were no known contaminants in the feed or water that would interfere with the objectives of the study.

ENVIRONMENTAL CONDITIONS
Temperature (°C): 21 - 22
Humidity (%): 54 - 78
Air changes (per hr): >= 10 (no air recirculation)
Photoperiod (hrs dark/hrs light): 12/12


IN-LIFE DATES: From: 06 July 2021 To: 04 Augustus 2021

Type of coverage:

semiocclusive

Vehicle:

water

Remarks:

(Elix)

Details on dermal exposure:

TEST MATERIAL
The test substance was ground to a powder using a mortar and pestle prior to weighing. The weighed samples of the test substance were kept at room temperature and dosed within 4 hours after removal from the storage container. Based on the test item data provided by the Sponsor, it was considered that the test item remained stable during this relatively short time period. The samples were applied after moistening with 0.3 mL water (Elix), to ensure close contact to the skin.

TEST SITE
Area of exposure: 18 cm^2
% coverage: approx. 10% of the total body surface
Type of wrap if used: a surgical gauze patch (Surgy 1D), successively covered with Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages.

REMOVAL OF TEST SUBSTANCE
- Washing: water
- Time after start of exposure: 24 hours

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

3 females

Control animals:

not required

Details on study design:

RANGEFINDING STUDY
A range finding study was performed in order to select the dose causing no mortality or significant toxicity to be used in the main study. One animal was dosed at 2000 mg/kg bw.

MAIN STUDY
- Duration of observation period following administration: 14 days
- Frequency of observations: on the day of dosing (at least three times) and once daily thereafter
- Mortality: twice daily
- Body weights: on day 1 (pre-dose), 8 and 15
- Irritation: The skin reactions were assessed approximately 24, 48 and 72 hours after the removal of the dressing and test item and thereafter once daily. Adjacent areas of untreated skin of each animal served as controls.
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No signs of systemic toxicity were observed.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Other findings:

No irritation was noted for any of the animals at any time point

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of an acute dermal study, performed according to OECD guideline 402 and in accordance with GLP principles, the dermal LD50 value of the test substance in female Wistar Han rats was determined to exceed 2000 mg/kg bodyweight. As a consequence, the test substance is not classified according to CLP criteria.

Executive summary:

The objective of this study was to determine the potential toxicity of ScFOS, when given by a single dermal dose.
The study was carried out according to the guidelines  OECD No. 402 (2017) "Acute Dermal Toxicity".

Initially, ScFOS was administered to a single female Wistar Han rat by a single dermal application at 2000 mg/kg body weight for 24 hours in a range finder study.
Based on the results, the main study was performed by dosing two additional females at 2000 mg/kg. All animals were subjected to daily observations and weekly determination of body
weight. Macroscopic examination was performed after terminal sacrifice (Day 15).
No mortality occurred.
No signs of systemic toxicity were noted in any of the animals. Furthermore, no irritation was noted for any of the animals at any time point.
The body weight gain shown by the animals during the observation period was within the range expected for rats used in this type of study.
No abnormalities were found at macroscopic postmortem examination of the animals.
The dermal LD50 value of Fructo-oligosaccharides in Wistar Han rats was established to exceed 2000 mg/kg body weight.

Based on these results, ScFOS does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2017) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Additional information

Acute oral toxicity: an experimental study performed under GLP compliance and in accordance with a method similar to a OECD TG 420 was flagged as a key study and assigned a Klimisch score of 2. 

Acute dermal toxicity: an experimental study performed under GLP compliance and in accordance with OECD TG 402 was flagged as a key study and assigned a Klimisch score of 1.

Justification for classification or non-classification

Acute oral toxicity: Based on the available data, ScFOS is not classified for acute oral toxicity according to the CLP Regulation 1272/2008 as the LD50 is higher than 9000 mg/kg bw.

Acute dermal toxicity: Based on the available data, ScFOS is not classified for acute dermal toxicity according to the CLP Regulation 1272/2008 as the LD50 is higher than 2000 mg/kg bw.